A Study to Evaluate the Effects of 3 Months Dosing With GW856553, as Assessed FDG-PET/CT Imaging: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Effects of 3 Months Dosing With GW856553, as Assessed FDG-PET/CT Imaging (NCT00633022), a randomized phase 2 study. The primary outcome is Change From Baseline of Mean of Maximum Tissue to Background Ratio (TBR) in the Qualifying Artery, Following 12 Weeks of Treatment in the Setting of Chronic Statin Therapy.

2. Clinical Question

The registry record describes a phase 2 study sponsored by GlaxoSmithKline. Enrollment was 99 participants. The study dates are listed as starting on 2008-06-02, with primary completion on 2009-12-03, and the status is completed. The study title refers to GW856553, while the intervention descriptions identify losmapimod; the registry record uses both names.

3. Trial Design

This was a randomized, double-blind, placebo-controlled, parallel-group phase 2 study. Its stated purpose was to assess the potential anti-inflammatory effects of a 3-month treatment with GW856553, using FDG-PET/CT imaging of inflammatory activity in the aorta and carotid plaques. The posted intervention descriptions identify the active treatment as losmapimod.

Participants were assigned to one of two losmapimod schedules or placebo. The twice-daily regimen was 7.5 mg orally each morning and evening. The once-daily regimen was 7.5 mg in the morning, with a placebo tablet in the evening. The placebo group received a matching tablet in the morning and evening. The arm descriptions specify a treatment period of 12 weeks. The registry record does not report the randomization ratio or the method used to generate or conceal the allocation sequence.

The primary endpoint was change from baseline in mean maximum tissue-to-background ratio in the qualifying artery. Baseline was defined using measurements from Days -14 to -1, and the endpoint was assessed up to Week 12. The qualifying artery could be the left or right carotid artery or the ascending aorta, selected using the highest segmental mean maximum ratio at baseline, subject to a qualifying-segment threshold. The primary endpoint analysis used the pharmacodynamic population, and only participants with data at the indicated assessment time were analyzed.

The registry lists 99 enrolled participants. The primary endpoint arm summaries include 32 participants in each losmapimod group and 29 in the placebo group. These endpoint-analysis counts are not the same thing as the overall enrollment figure. Details about withdrawals, adherence, and the reasons participants did not contribute endpoint data are not reported in the registry record.

The record lists 10 outcome measures and 4 analyses overall. It includes a secondary imaging endpoint based on the most diseased segment, along with listed outcomes relating to hs-CRP, blood pressure, heart rate, ECG findings, laboratory abnormalities, and urinalysis. The original trial sample-size justification and its prespecified statistical plan are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Participants were randomized in the study to receive oral dose of Losmapimod 7.5 milligram (mg) twice daily, Losmapimod 7.5 mg once daily or placebo.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Pharmacodynamic (PD) Population comprised of all participants who provided PD data. Only those participants with data available at the indicated time points were analyzed.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline of Mean of Maximum Tissue to Background Ratio (TBR) in the Qualifying Artery, Following 12 Weeks of Treatment in the Setting of Chronic Statin Therapy, measured over Baseline (Days -14 to -1) and up to Week 12.

The primary endpoint measured change from baseline in the mean of the maximum tissue-to-background ratio, or TBR, in a qualifying artery. FDG-PET/CT was used to assess the imaging signal. TBR expresses tissue signal relative to background signal; as a general statistical and measurement concept, a ratio can make a tissue measurement interpretable in relation to a reference signal. In this study the imaging measure was intended to reflect inflammatory activity in the arteries.

The qualifying artery was selected from the left or right carotid artery or the ascending aorta. The registry definition selected the artery with the highest segmental mean maximum TBR at baseline. The qualifying segment was required to have a TBR of at least 1.6. If more than one artery met the criterion, the artery with the greatest mean maximum TBR was selected. Baseline was defined as the value from Days -14 to -1, and change was calculated by subtracting the baseline value from the individual post-treatment value.

Change from baseline is used to describe how the measured value at follow-up differs from the participant’s starting value. A negative group mean change indicates a decrease in the measured ratio on average; it does not, by itself, identify the reason for that change or show that participants experienced a clinical benefit. The primary endpoint is an imaging measure, not a direct measure of symptoms, function, or cardiovascular events. The registry record does not report evidence validating a particular size of change in this measure as clinically important.

The primary endpoint population comprised participants who provided pharmacodynamic data. Only participants with data at the relevant time point were analyzed. The registry record does not report further details of the missing-data approach or how the analysis handled participants without an observed value at that time point.

7. Results Posted in the Registry

• Losmapimod 7.5 mg Twice Daily: mean -0.15 versus -0.07 on control; difference -0.08 (95% CI -0.18 to 0.03), standardized effect d = -0.36; z-test p = 0.154.
• Losmapimod 7.5 mg Once Daily: mean -0.12 versus -0.07 on control; difference -0.05 (95% CI -0.14 to 0.04), standardized effect d = -0.30; z-test p = 0.242.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline of the 'Most Diseased Segment (MSD)' Average Maximum TBR in the Qualifying Artery Following 12 Weeks of Treatment With GW856553 or Placebo in the Setting of Chronic Statin Therapy

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Losmapimod 7.5 mg Twice Daily: mean -0.29 versus -0.22 on control; difference -0.07 (95% CI -0.21 to 0.06), standardized effect d = -0.27; z-test p = 0.295.
  • Losmapimod 7.5 mg Once Daily: mean -0.25 versus -0.22 on control; difference -0.03 (95% CI -0.16 to 0.10), standardized effect d = -0.11; z-test p = 0.656.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Losmapimod 7.5 mg Twice Daily and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Losmapimod 7.5 mg Once Daily and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists a range of secondary outcomes, including another FDG-PET/CT measure based on the most diseased segment, hs-CRP, blood pressure, heart rate, ECG findings, and laboratory and urinalysis results. A total of 9 secondary outcomes are posted. The numerical summaries and comparisons included in the registry record for the most diseased segment imaging endpoint show the same general pattern as the primary endpoint: the estimated contrasts favor lower mean changes in the losmapimod groups, but the intervals include zero and the estimates are uncertain.

This broad consistency between the two posted imaging measures does not independently establish a treatment effect. The measures are related imaging outcomes from the same study population and cannot be treated as independent confirmations. In addition, the registry does not provide numerical results for every listed secondary outcome in the information summarized in the record, so no overall conclusion about all secondary outcomes can be drawn from the listed outcome names alone.

Secondary results generally carry less weight than a prespecified primary analysis when many outcomes or comparisons are examined. As a general statistical principle, testing multiple hypotheses increases the chance that some results appear notable by chance, unless the analysis plan accounts for multiplicity. The registry record does not report whether multiplicity adjustment was planned or applied to the secondary analyses. Their estimates can help describe the pattern and generate questions for further study, but they should not override the uncertain primary result or be interpreted as confirmatory evidence on their own.

The registry lists outcomes involving safety measurements and laboratory findings as well as efficacy-related measures. These serve different purposes and may have different analysis scales. The record does not report a complete prespecified hierarchy or a detailed plan for interpreting them together. Accordingly, the secondary findings should be considered exploratory unless the registry identifies a specific confirmatory role, which it does not do in the posted information.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Baseline of the 'Most Diseased Segment (MSD)' Average Maximum TBR in the Qualifying Artery Following 12 Weeks of Treatment With GW856553 or Placebo in the Setting of Chronic Statin Therapy
• Change From Baseline in Blood Concentration of High Sensitivity C-reactive Protein (Hs-CRP)
• Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points
• Mean Heart Rate at Indicated Time Points
• Number of Participants With 12-lead Electrocardiogram (ECG) Findings
• Number of Participants With Clinical Chemistry Abnormalities of PCI
• Number of Participants With Hematology Abnormalities of PCI
• Number of Participants With Urinalysis Dipstick Results

9. Statistical Interpretation

10. Statistical Methods Explained

What does a group mean describe?

The primary endpoint is continuous: each participant has a numerical change in TBR, and the registry reports the mean and standard deviation for each arm. A mean gives the average observed change among analyzed participants. It can summarize the group while hiding differences among individuals, so it should be read together with the standard deviation and the uncertainty around a treatment-versus-placebo estimate. The endpoint means are -0.146, -0.122, and -0.07 for the two losmapimod regimens and placebo, respectively. The standard deviations indicate that participant measurements varied within each arm.

A mean difference compares the average in one arm with the average in another. The recalculated contrasts are unadjusted comparisons derived from the posted summary statistics. For the primary endpoint, the twice-daily versus placebo contrast is -0.076 and the once-daily versus placebo contrast is -0.052. The negative signs indicate that the active-arm mean changes are lower than the placebo mean change in these comparisons. The size of the difference is expressed in the endpoint’s measurement scale, not as a percentage or a standardized clinical effect.

Why distinguish the recalculation from ANCOVA?

An unadjusted comparison uses the reported group summaries without accounting for other variables. ANCOVA, or analysis of covariance, is a general method for comparing outcomes while adjusting for specified covariates. The registry identifies the sponsor’s method as ANCOVA and labels the reported parameter as a mean difference in final values. The registry record does not identify the covariates used, the model specification, or the handling of missing observations. Consequently, the sponsor’s adjusted estimate and the recalculated unadjusted estimate answer related but not identical statistical questions. Their estimates need not match exactly.

The recalculated p-values are 0.154 and 0.242 for the primary endpoint comparisons. A p-value describes how compatible the observed data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. In general, a p-value alone does not communicate the range of effect sizes that remain plausible; the interval estimate is needed for that context.

What does an interval communicate?

A confidence interval gives a range of estimates compatible with the data under the method’s assumptions and stated confidence level. The sponsor reports 95% confidence intervals for the primary ANCOVA comparisons. Each includes zero, the value corresponding to no mean difference. This indicates that the posted results do not sharply separate the groups on the primary endpoint. It does not establish that the true effect is exactly zero. The recalculated interval bounds are not repeated in this explanation, but they likewise include zero.

Precision is affected by both the amount of information and the variability of the outcome. In general, more observations can make an estimate more precise, while greater variability can make it less precise. The endpoint analysis has 32 participants in each active arm and 29 in placebo, and the observed standard deviations are not negligible relative to the estimated contrasts. This context helps explain why the treatment comparisons remain uncertain, but it does not justify a new calculation of power or a claim about the trial’s original design.

Why can over-dispersion matter?

Over-dispersion is a general statistical issue in which observed variation is greater than a model expects. If a model understates variation, standard errors can be too small and uncertainty can appear narrower than warranted. The primary outcome is a continuous imaging measure, and the registry reports standard deviations. The posted record does not state that over-dispersion was detected or that a special correction was used. It should therefore be treated as a general modeling consideration, not as a reported feature of this trial.

How should the endpoint population be understood?

The primary endpoint was analyzed in the pharmacodynamic population, described as participants who provided pharmacodynamic data, with only those having data at the indicated time points analyzed. This is not a statement that every randomized participant contributed an endpoint value. The registry record does not report the full participant flow for this endpoint, the reasons for missing measurements, or the method used to address missing data. Those omissions matter because the analyzed group may differ from the full randomized group if data availability is related to outcomes or treatment.

The registry lists a parallel-group randomized design and double masking. Randomization is intended, in general, to reduce systematic differences between treatment groups at baseline, while masking can reduce certain sources of bias in treatment delivery and outcome assessment. The record does not give enough operational detail to assess how either feature was implemented. The primary imaging outcome also depends on artery selection and image measurement rules; the record describes the qualifying-artery definition but does not report reader masking or reproducibility information.

The sponsor’s reported ANCOVA and the summary-based recalculations should therefore be read as complementary descriptions rather than interchangeable analyses. The sponsor’s estimates reflect the registry’s named analysis method, while recalculated estimates are simple, unadjusted summaries. The registry record does not report a prespecified hierarchy of analyses, an interim-analysis plan, or a detailed statistical analysis plan. Those items should not be inferred from the fact that specific analyses appear in the posted results.

11. Confidence Intervals and Precision

Precision concerns how tightly an estimate is determined by the observed data. The sponsor-reported primary ANCOVA estimate for twice-daily losmapimod versus placebo is -0.04, with a 95% confidence interval from -0.14 to 0.06. For once-daily losmapimod versus placebo, the estimate is -0.02, with a 95% confidence interval from -0.11 to 0.06. Each interval crosses zero, so the data are compatible with no mean difference as well as with values on either side of zero within the interval.

The confidence intervals are not guarantees that the true effect lies in the stated range. They express uncertainty under the analysis method and its assumptions. Their width also matters: an interval can include zero while still allowing differences that may be relevant to interpretation. The registry record does not specify a threshold for a clinically important change in the imaging measure, so the intervals cannot be judged against such a threshold from the posted information alone.

The recalculated estimates are unadjusted mean differences of -0.076 and -0.052. Their recalculated intervals also include zero. The sponsor’s ANCOVA estimates differ in magnitude from these summary-based estimates, which is possible because adjustment and the definition of the reported parameter differ. The sponsor estimates and confidence intervals should be read as the registry’s reported adjusted results; the recalculations are not a replacement for them.

The number of analyzed participants and variation in the endpoint affect precision. The primary endpoint summaries include 32 participants in each losmapimod group and 29 in placebo. The standard deviations are 0.248, 0.184, and 0.163. These features provide context for the uncertainty but do not, on their own, reveal whether the original study was adequately sized. Its original sample-size assumptions and justification are not reported in the registry record.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the trial’s original design calculations. For this continuous endpoint, the reported figures are participants per arm, not total events. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as the stated fraction of the observed effect. The trial’s own original design assumptions are not reported in the registry record.

The 80% power column gives the planned number of participants per arm under those assumptions for an analysis with an 80% chance of detecting an effect of the specified size, if that effect and the planning model are correct. The 90% power column gives the corresponding number per arm for a higher chance of detection under the same assumptions. These are hypothetical planning calculations, not observed outcomes of the completed study.

For the primary contrast of twice-daily losmapimod versus placebo, planning for 100% of the observed effect gives 123 participants per arm for 80% power and 164 for 90% power. Planning for 75% of the observed effect gives 218 and 292 participants per arm; planning for 50% gives 490 and 656 per arm. For once-daily treatment versus placebo, the corresponding values are 177 and 237, then 314 and 421, then 707 and 946 participants per arm.

The pattern reflects a general principle: smaller effects are harder to distinguish from random variation, so detecting them at the same power generally requires more participants. These calculations use effects observed in this trial, which are uncertain estimates and may not represent the effect in another study. This is not observed power.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.076; pooled standard deviation σ = 0.212.
2. n = 2 × (1.96 + 0.842)² × 0.212² / -0.076² = 122.4, rounded up to 123 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.076                      # observed difference in means
sigma <- 0.212211850896732                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(633022)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 123 (80% power), 164 (90% power)
 75% of observed effect: n per arm = 218 (80% power), 292 (90% power)
 50% of observed effect: n per arm = 490 (80% power), 656 (90% power)
power.t.test: 123.4 
Simulated power at n = 123 per arm: 0.800 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparisons using ANCOVA, with the parameter described as a mean difference in final values. For twice-daily losmapimod versus placebo, the reported estimate is -0.04 and the 95% confidence interval is -0.14 to 0.06. For once-daily losmapimod versus placebo, the estimate is -0.02 and the 95% confidence interval is -0.11 to 0.06. Both intervals include zero. The registry also reports p-values for these analyses.

The recalculated comparisons use the posted arm means and standard deviations to make simple unadjusted comparisons. They estimate mean differences of -0.076 for twice-daily treatment and -0.052 for once-daily treatment, with unadjusted p-values of 0.154 and 0.242. The recalculations are not the sponsor’s ANCOVA and should not be treated as a correction to it. Adjustment and the distinction between change summaries and final-value estimates can lead to different results.

The record does not flag a discrepancy between the posted sponsor analyses and the recalculations. The sponsor results remain the registry’s reported adjusted analyses, while the recalculations offer a separate, transparent comparison based on summary statistics. The covariates and full model details for ANCOVA are not reported in the registry record, limiting a more detailed reconciliation.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint and lists secondary outcomes, but it does not report a detailed statistical analysis plan or a multiplicity strategy. Multiplicity arises when investigators evaluate several outcomes, treatment comparisons, or time points. As a general statistical principle, a larger set of tests creates more opportunities for chance findings. Methods such as adjusting significance thresholds or organizing outcomes in a prespecified hierarchy can address this issue, but whether such methods were used in this trial is not reported in the registry record.

The primary endpoint analysis population is described as the pharmacodynamic population, consisting of participants who provided pharmacodynamic data; only participants with data at the indicated time points were analyzed. The primary endpoint summaries include 32 participants in each active arm and 29 in placebo. The registry reports total enrollment of 99, but it does not provide a complete flow from randomized participants to those included in each endpoint analysis in the information.

The registry record does not report the reasons for missing measurements, whether missingness differed by group, or the method used to handle missing data. It also does not report sensitivity analyses that might assess how missing outcomes affect the estimates. This limits assessment of whether the endpoint analysis represents all randomized participants or only those with available measurements at the relevant time.

The sponsor’s primary analyses are identified as ANCOVA, but covariates, model details, and assumptions are not reported. Interim analyses, stopping rules, and the original sample-size justification are also not reported in the registry record. These absences do not show that such procedures were or were not used; they mean the posted record does not establish them. Interpretation should therefore focus on the analyses and populations actually described, without assuming unreported design or analysis choices.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: presyncope (3.1%), road trafic accident (3.1%), bundle branch block left (3.1%), dizziness (3.0%), hyperhidrosis (3.0%).

The registry reports serious adverse events and other adverse events by treatment group. Among participants at risk for serious adverse events, the counts with such events were 4 of 34 in the twice-daily losmapimod group, 1 of 33 in the once-daily group, and 3 of 32 in the placebo group. The registry reports deaths of 0, 0, and 1 in those groups, respectively. These are counts from the posted record; they do not establish why an event occurred or whether it was caused by treatment.

For other adverse events, the counts were 25 of 34, 24 of 33, and 28 of 32 in the same order of groups. The registry also lists serious-event terms, including presyncope, road trafic accident, left bundle branch block, dizziness, hyperhidrosis, and vomiting. The record gives percentages for these terms, but the definitions and event-level details are not reported in the material.

Adverse-event counts should be interpreted descriptively. The group sizes are limited, and the registry record does not provide a statistical comparison or enough information about event timing, severity beyond the serious-event classification, or attribution. These numbers do not by themselves establish comparative safety.

17. What the Result Does, and Does Not, Mean

The posted results describe average changes in an imaging measure after 12 weeks in participants with available pharmacodynamic data. The mean change was negative in all three groups, including placebo. The unadjusted contrasts and sponsor-reported ANCOVA estimates point toward lower values in the losmapimod groups than in placebo, but the estimates are uncertain: the sponsor’s 95% confidence intervals include zero, and the recalculated intervals do as well.

This pattern should not be translated into a claim that either regimen does or does not affect atherosclerosis or clinical outcomes. TBR is an imaging measure selected to assess inflammatory activity. The registry record does not show that a particular change in TBR predicts fewer cardiovascular events, improved symptoms, or another patient-important outcome. It also does not report a threshold for a clinically meaningful change.

An interval that includes zero does not prove that there is no effect. It indicates that the data do not precisely distinguish the estimated difference from no difference under the stated analysis. Conversely, a directionally lower point estimate is not proof of a treatment effect. The confidence intervals leave uncertainty about the size and direction of the true difference.

The study is a phase 2 trial with endpoint analyses in a pharmacodynamic population, not a report of long-term clinical outcomes. The registry record does not provide the original sample-size justification, complete missing-data details, or a full statistical analysis plan. These limitations constrain how confidently the estimates can be generalized or interpreted. The results are a description of the posted study findings, not medical advice or a basis for an individual treatment decision.

18. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the distinction between a group’s observed change and the treatment-versus-placebo contrast. Each arm had a negative mean change in the primary imaging measure, but the question of interest is whether the change differed between arms. The relevant estimates are the between-group contrasts, together with their uncertainty, rather than whether an individual arm’s mean change is above or below zero.

It also demonstrates why an adjusted analysis and a summary-based recalculation can produce different estimates. The sponsor’s ANCOVA compares final values using an adjusted model, while the recalculations are unadjusted comparisons from posted summary statistics. Neither should be silently substituted for the other. Reading both makes clear what can be learned from the registry record and what remains dependent on unreported model details.

The study highlights the importance of endpoint choice. FDG-PET/CT provides an imaging outcome related to the study’s intended assessment of arterial inflammatory activity, but an imaging endpoint is not itself a clinical event. Interpretation requires care about what the measurement represents and whether a change has established clinical meaning; that latter evidence is not reported in the registry record.

Finally, the study’s planning illustrations show how assumptions about the effect to detect shape participant-number requirements. Smaller target effects require larger planned group sizes under the stated assumptions. Those illustrations cannot be used to infer that the completed trial was adequately or inadequately powered, because its original design justification is not reported. Together, these features make the record useful for teaching the difference between effect estimates, precision, analysis choices, and planning calculations.

19. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations specific to this record affect interpretation. The primary analysis includes participants with available pharmacodynamic data at the relevant time point, rather than an explicitly described analysis of every randomized participant. Although the primary endpoint arm counts are posted, the record does not explain the participant flow, the reasons for missing measurements, or whether missingness differed across arms. The impact of these omissions cannot be determined from the posted information.

The primary measure is an imaging ratio in a qualifying artery selected using baseline imaging. The registry describes the artery-selection rule and baseline threshold, but it does not report image-reading reproducibility, reader masking, or the clinical significance of a given change. The endpoint therefore has a defined measurement procedure in the record, but its connection to patient-important outcomes is not established there.

The sponsor reports ANCOVA, yet the covariates and model specification are not reported. The posted summary-based recalculations are unadjusted and differ in their estimand from the reported final-value analyses. This prevents a full technical reconciliation of the two sets of estimates. The original sample-size rationale, planned detectable effect, and statistical analysis plan are also not reported.

The registry lists multiple secondary outcomes, but it does not report a multiplicity strategy. This makes secondary findings harder to interpret as confirmatory evidence. Safety results are presented as event counts, without detailed timing, attribution, or comparative statistical analyses in the posted information. Finally, the study is described as phase 2 and assessed a 12-week treatment period; the registry record does not report long-term clinical outcomes in the information.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study to Evaluate the Effects of 3 Months Dosing With GW856553, as Assessed FDG-PET/CT Imaging — NCT00633022.
• Registry record last updated 2018-10-17; status last verified 2018-08.
• Results first posted 2018-10-17.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

NCT00633022 is a completed, randomized, double-blind, placebo-controlled, parallel-group phase 2 study sponsored by GlaxoSmithKline. It enrolled 99 participants with established atherosclerosis and assessed two 12-week losmapimod regimens against placebo in the setting of chronic statin therapy.

The primary endpoint was change from baseline in mean maximum TBR in a qualifying artery, assessed by FDG-PET/CT. The posted group means were negative in all arms. Both sponsor-reported ANCOVA confidence intervals and the unadjusted recalculated intervals include zero, leaving uncertainty about the between-group differences.

The record includes a secondary imaging outcome and lists additional clinical and safety measures. It does not report the original sample-size justification, complete missing-data methods, full ANCOVA specification, or multiplicity plan. The findings describe the posted imaging and adverse-event data and do not establish effects on clinical outcomes.